AstraZeneca Wins $5 Billion-Plus Cancer Drug Patent Battle Over Tagrisso
AstraZeneca
Biopharmaceutical Manufacturer
Pfizer
Pharmaceutical R&D Developer
Recently, the long-standing patent battle between Pfizer and AstraZeneca (AZ) has finally come to an end. According to Reuters, a federal judge in Delaware overturned the jury's decision that AstraZeneca's Tagrisso (osimertinib) should pay $107.5 million for infringing Pfizer's cancer drug Nerlynx (neratinib) patent. Judge Matthew Kennelly believed that Pfizer's accusation against AstraZeneca's best-selling drug...Lung CancerThe drug Tagrisso infringes on its two invalid patents.
The Reversed Outcome of the Patent War
Neratinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that irreversibly binds to EGFR (HER1), HER2, and HER4, inhibiting receptor phosphorylation and subsequently blocking downstream signal transduction. Ultimately, it can inhibit cancer cell proliferation, survival, migration, etc., and improve the tumor microenvironment.
In 2009, Pfizer acquired Wyeth for $68 billion, bringing Neratinib into its portfolio. In 2011, Puma Biotechnology obtained the license for Neratinib from Pfizer and assumed full responsibility for the global development and commercialization of the drug.
In July 2017, Neratinib was approved by the FDA for marketing to reduce the risk of recurrence in early-stage HER2-positive breast cancer. In 2020, the FDA approved Neratinib in combination with Capecitabine for adult patients with advanced or metastatic HER2-positive breast cancer who had previously received two or more prior therapies. With the approval of this indication, Neratinib can be used not only for early-stage breast cancer patients but also for those with advanced or metastatic breast cancer.
Osimertinib is a third-generation EGFR-TKI developed by AstraZeneca. It was approved by the FDA in November 2015 for second-line treatment of T790M mutation-positive (T790M+) NSCLC patients and has since been approved for multiple indications in the NSCLC field. As a third-generation EGFR-TKI on the market, osimertinib's sales have continuously broken records, reaching $5.799 billion in 2023, making it AstraZeneca’s top product.
In 2021, Pfizer's subsidiary Wyeth and Puma Biotechnology began suing AstraZeneca, alleging that osimertinib infringed on two key patents: the “314 Patent,” which involves a method of treating NSCLC patients resistant to gefitinib and/or erlotinib using an EGFR blocker covalently bound to the cysteine 773 residue of a protein.
Another is Wyeth's "162 Patent," which protects the use of these irreversible inhibitors for treating NSCLC patients carrying the specific T790M mutation on the EGFR protein who are resistant to gefitinib or erlotinib.
In May 2023, a federal jury in Delaware ruled that AstraZeneca did infringe on Pfizer's patent and set the compensation amount at $107.5 million. Although AstraZeneca argued that Pfizer's patent was invalid, the jury remained unmoved. In response to this outcome, AstraZeneca proposed an "additional defense."
In this latest ruling, the judge found Pfizer's claim that osimertinib infringes on its two patents invalid. This is because the patents lacked an effective written description of their invention, and scientists of ordinary skill in the field would be unable to recreate them.
AstraZeneca ultimately won a reversal in this patent war, achieving victory. But for Osimertinib, it faces many challenges.
EGFR-TKI: Large Market, Strong Competition
Currently, lung cancer is the second most common cancer globally. According to data from the International Agency for Research on Cancer (IARC) of the World Health Organization, in 2020, lung cancer accounted for 11.1% of all cancer types worldwide. Among lung cancer patients, 85% have non-small cell lung cancer (NSCLC), and the remaining 15% have small cell lung cancer (SCLC). EGFR is one of the most important oncogenic driver genes in NSCLC. Studies show that the mutation rate of EGFR in global metastatic NSCLC patients is 30%. In Chinese NSCLC patients, the proportion of EGFR mutations is approximately 51%.
EGFR-TKI is the standard therapy for EGFR-mutant NSCLC patients.
As of now, three generations of EGFR-TKI products have been approved globally. The first and second generations of EGFR-TKIs are mainly used for patients with EGFR exon 19 deletion mutations (EGFR ex19del) and exon 21 L858R mutations (EGFR 21L858R). The third-generation drugs, in addition to targeting sensitive mutations, are also effective against the T790M mutation, which causes acquired resistance to first- and second-generation TKIs.
As an approved EGFR-TKI, osimertinib has continuously set new sales records since its market launch, becoming a key driver of AstraZeneca's performance. However, while the third-generation EGFR-TKI market is vast, the competition is also intense, with seven similar products approved globally and six approved in China.
In addition, the domestic compound patent CN103702990 for Osimertinib will expire in July 2032. As a product with huge market potential among imported anti-cancer drugs in China, the generic version of Osimertinib developed by Jiangsu Wanbang Biopharmaceutical Group has been submitted for marketing approval as a Category 4 generic drug and has been successfully approved.
In terms of innovative drugs, Jiangsu Hansoh Pharmaceutical's Almonertinib and Allist Pharmaceuticals' Furmonertinib have been approved for marketing by the NMPA. In addition, Aosaikang's Limertinib, Johnson & Johnson's Lazertinib, Tongyuan Kang Pharmaceutical’s TY-9591, and Ace Life Pharmaceuticals' Avitinib have either submitted marketing applications in China or entered Phase III clinical trials.
In addition to competition from similar products, osimertinib also faces challenges from bispecific antibodies. Recently, in a head-to-head clinical trial comparing Johnson & Johnson's EGFR/C-MET bispecific antibody amivantamab combined with the 3rd generation EGFR-TKI lazertinib (A+L) versus osimertinib monotherapy for first-line treatment of EGFR+ advanced NSCLC, the PFS endpoint was achieved. Results showed that, compared to osimertinib, the A+L group significantly reduced the risk of PFS by 30% (HR, 0.70; 95% CI, 0.58–0.85; P<0.001), with mPFS reaching 23.7 months (vs 16.6 months) and ORR reaching 86% (vs 85%). In terms of OS, the median OS in the A+L group could not be estimated (HR, 0.77), while the osimertinib group reached 37.3 months (HR, 0.77). OS reached a statistically significant endpoint. A+L has the potential to become the new standard for first-line treatment of EGFR+ NSCLC.
In generic drugs andInnovative DrugUnder the siege, AstraZeneca's Osimertinib is facing fierce competition. Anyway, the victory of this patent war has saved AstraZeneca $107 million in compensation.
Reference Source:
1、https://www.fiercepharma.com
2、Xuhong JC,Qi XW,Zhang Y,et al.Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer.[J].Am J Cancer Res,2019,10:2103-2119.
3. CDE Official Website
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